TY - JOUR T1 - Evaluation of succinimidoethyl and pivaloyloxyethyl esters as progenitors of methyldopa in man, rhesus monkey, dog, and rat. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 640 LP - 646 VL - 6 IS - 6 AU - S Vickers AU - C A Duncan AU - S D White AU - G O Breault AU - R B Royds AU - P J de Schepper AU - K F Tempero Y1 - 1978/11/01 UR - http://dmd.aspetjournals.org/content/6/6/640.abstract N2 - The succinimidoethyl (Sm) and pivaloyloxyethyl (P) esters of methyldopa were evaluated as progenitors of the latter. Experiments in spontaneously hypertensive (SH) rats and humans demonstrated that a radioactive dose of progenitor was well absorbed. The metabolism of these progenitors appeared to be comparable in the SH rat; the urinary excretion of [3H]methyldopa was similar after oral administration of [3H]Sm or [3H]P. In humans the levels of [3H]methyldopa were higher in the urine following administration of [3H]P. Apparently Sm was more resistant than P to extrahepatic esterase action in man (and dog). In man the catechol nucleus of Sm was apparently conjugated prior to hydrolytic cleavage to release conjugated [3H]methyidopa. The progenitors possessed similar antihypertensive properties in the SH rat but preliminary results in humans suggested that Sm possessed less antihypertensive potency than P. ER -